Introduction. Сombination of alpelisib plus fulvestrant is approved in patients with hormone receptor positive, HER2-negative, PIK3CA-mutated advanced breast cancer (ABC) after progression on hormonotherapy. Efficacy data of alpelisib in heavily pretreated patients with HR+/HER-2-, PIK3CA-mutated advanced breast cancer are limited, only results from phase I trial are available. Here we report our results of alpelisib efficacy in 19 heavily pretreated patients.Object: to evaluate efficacy and safety of combination alpelisib plus fulvestrant in patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer in initial and later lines of therapy in real clinical practice.Materials and methods. Combination of  alpelisib plus fulvestrant was investigated in  19  patients with HR+/HER2-, PIK3CAmutated ABC, alpelisib at a dose of 300 mg per day plus fulvestrant at a dose of 500 mg i.m. every 28 days and once on day 15. Treatment continued until disease progression or unacceptable toxicity.Results. From February 2021 19 patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer were treated with alpelisib plus fulvestrant. The data cut off is October 2021. Median lines of treatment in advanced disease was five, including 19 (100%) patients received CDK4/6, 14 (74%) – fulvestrant and/or everolimus and 15 (79%) – chemotherapy. 4 (21%) received alpelisib in a second line, 15 (79%) – in subsequent lines. Median progression-free survival was 7 months. The response was evaluated in 18 patients: partial response was achieved in 5 (28%) patients, stable disease – in 9 (50%), disease progression – 4 (22%). The most frequent adverse events were hyperglycemia – 74% (grade 3 – 22%), creatinine increased – 42% and rash – 37% (grade 3 – 22%). Only one patient has discontinued the treatment due to Quincke`s edema.Conclusions. Combination of alpelisib with fulvestrant is an effective option both in initial and later lines of therapy in patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer including fulvestrant, CDK4/6 inhibitors and/or everolimus – pretreated patients.

e12586 Background: TCHP is the standard regimen for neoadjuvant therapy (NAT) of HER2-positive early breast cancer (HER2+ eBC) and requires primary G-CSF prophylaxis (PP). Pathological complete response (pCR) after NAT reflects better pts outcomes. Long-acting G-CSF presents more balanced neutrophils (NEU) count vs short G-CSF. Preclinical data show tumor-associated neutrophils (TANs) as anti-tumor effector cells in eBC. There are limited data on the clinical benefit of TCHP in the subset of patients with HER2 amplification by ISH in the low-moderate of HER2 protein expression. This sub-group analysis of multicenter prospective study was designed to evaluate the pCR after TCHP with PP by empegfilgrastim (E) or filgrastim (F) in pts with HER2+ eBC. Methods: HER2+ eBC pts (n=199) with II-III stages are getting NAТ: 6 docetaxel/ carboplatin/ trastuzumab + pertuzumab + empegfilrastim/ filgrastim (TCHP+E/F). Short G-CSF (F) uses according to routine clinical practice, long-acting G-CSF (E) - 24h after each NAT cycle. This descriptive analyse were performed for pts who completed the whole NAT regimen. The study endpoints: pCR (ypT0/is, ypN0) in intention-to-treat (ITT) population and according to HER2 status: 3+ vs 2+ ISH positive (+). ClinicalTrials.gov No NCT04905329. Results: At the data cut-off (01’2023) 199 pts with HER2+ BC completed planned NAT and surgery (71 pts – TCHP+E; 128 pts – TCHP+F). pCR rate according to HER2 status and in ITT population in 2 G-CSF groups is presented. In TCHP+E group pCR rate exceeds KRISTINE trial data despite a more enriched pts’ population with poor prognosis (34% pts with IIIB - IIIC vs 17% pts in KRISTINE trial) while TCHP+F showed comparable results with historical control. The superior pCR rate under PP with E was also observed in HER2 (3+) pts sub-group vs PP with F. However, in HER2 (2+ ISH+) the results are similar in 2 G-CSF groups. The mature data are awaited. Conclusions: TCHP+E shows superior pCR rate vs TCHP+F in the ITT and HER2 (3+) population. The obtained results affirm data of preclinical research on the ability of G-CSF to switch tumor immunity from “cold” to “hot” in the eBC. We assumed that balanced NEU count under long-acting G-CSF stimulation enhances TANs infiltration is increasing therapy efficiency. In HER2 (2+ ISH+) population pCR results were comparable in 2 G-CSF groups. Discrepancies between gene amplification and protein overexpression resulted in declined amount of HER2-inhibitors-HER2 receptor active complexes. It can be TANs failure to kill anti-HER2-antibody-opsonized cancer cells by a trogoptosis. Our hypothesis requires further confirmation with translational research. Clinical trial information: NCT04905329 . [Table: see text]